Université Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, CNRS EAC4413, 75013, Paris, France.
Biochem J. 2012 Jul 15;445(2):219-28. doi: 10.1042/BJ20120528.
Legionella pneumophila is an opportunistic pathogen and the causative agent of Legionnaires' disease. Despite being exposed to many chemical compounds in its natural and man-made habitats (natural aquatic biotopes and man-made water systems), L. pneumophila is able to adapt and survive in these environments. The molecular mechanisms by which this bacterium detoxifies these chemicals remain poorly understood. In particular, the expression and functions of XMEs (xenobiotic-metabolizing enzymes) that could contribute to chemical detoxification in L. pneumophila have been poorly documented at the molecular and functional levels. In the present paper we report the identification and biochemical and functional characterization of a unique acetyltransferase that metabolizes aromatic amine chemicals in three characterized clinical strains of L. pneumophila (Paris, Lens and Philadelphia). Strain-specific sequence variations in this enzyme, an atypical member of the arylamine N-acetyltransferase family (EC 2.3.1.5), produce enzymatic variants with different structural and catalytic properties. Functional inactivation and complementation experiments showed that this acetyltransferase allows L. pneumophila to detoxify aromatic amine chemicals and grow in their presence. The present study provides a new enzymatic mechanism by which the opportunistic pathogen L. pneumophila biotransforms and detoxifies toxic aromatic chemicals. These data also emphasize the role of XMEs in the environmental adaptation of certain prokaryotes.
嗜肺军团菌是一种机会致病菌，也是军团病的病原体。尽管在其自然和人为栖息地（自然水生生物区系和人为水系统）中接触到许多化学化合物，但嗜肺军团菌能够适应和在这些环境中生存。该细菌解毒这些化学物质的分子机制仍知之甚少。特别是，在分子和功能水平上，对于能够有助于嗜肺军团菌化学解毒的 XMEs（外来生物代谢酶）的表达和功能，记录很少。在本文中，我们报告了三种已鉴定的嗜肺军团菌临床株（巴黎、 Lens 和费城）中独特乙酰转移酶的鉴定和生化及功能特征。该酶是芳香胺 N-乙酰转移酶家族（EC 2.3.1.5）的一个非典型成员，在该酶中存在菌株特异性序列变异，产生具有不同结构和催化特性的酶变体。功能失活和互补实验表明，这种乙酰转移酶使嗜肺军团菌能够解毒芳香胺类化学物质并在其存在下生长。本研究提供了一种新的酶促机制，通过该机制，机会致病菌嗜肺军团菌可以转化和解毒有毒的芳香化学物质。这些数据还强调了 XMEs 在某些原核生物的环境适应中的作用。
